The objective of these studies is to examine the influence of intestinal absorption. The intestine is both a metabolic and an absorptive organ, and the intestinal villus cell adapts in response to luminal and metabolic stimulation. While these stimuli interact in the enterocyte, there are few data which correlate intestinal metabolism with absorption. I have shown that rats maintained in positive metabolic balance, using total parenteral nutrition, absorb more glucose than fasted rats, despite equivalent brush border glucose transport activity in the two groups. The hypothesis to be tested is that the activity of the metabolic pathways in the villus cell influences the rate of disposal of absorbed solute which in turn can affect the rate of solute uptake from the intestinal lumen. This hypothesis will be tested in rats and humans using lactose as a model substrate. The steady state absorption of lactose by rat jejunum in vivo will be measured, and the ability of dietary and metabolic manipulations to alter lactose absorption will be tested. The results will be compared to measurements of mucosal lactase specific activity, glucose and galactose metabolizing enzyme specific activities and the absorption of glucose and galactose, the lactose hydrolytic products. The metabolic disposition of glucose and galactose by the intestinal mucosa after lactose perfusion will be examined in later studies. Studies of lactose absorption by human subjects will be performed using a breath hydrogen excretion test that will be modified to allow the determination of intestinal lactose absorption capacity. Determination of absorption capacity will be made before and after specific dietary manipulations in an attempt to demonstrate functional adaptation by the intestine. The combined results of the animal and human studies should demonstrate whether or not an induced alteration in villus cell metabolism can affect solute absorption. The results also might suggest that the ability to change carbohydrate absorption by manipulating intracellular enzyme activity is of benefit in the management of malnutrition.